Glycolytic inhibition: an effective strategy for developing calorie restriction mimetics
Glycolytic inhibition: an effective strategy for developing calorie restriction mimetics
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DOI：
10.1007/s11357-020-00298-7
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发表时间：
2020-11-12
期刊：
影响因子：
5.6
通讯作者：
Roth, George S.
中科院分区：
文献类型：
--
作者：
Ingram, Donald K.;Roth, George S.
卡路里限制模拟物涵盖了一个不断增长的研究领域，旨在开发模拟长期卡路里限制的抗衰老作用而不需要改变饮食习惯的治疗方法。已经鉴定了广泛的方法，包括（1）脂肪和碳水化合物代谢的肠抑制剂;（2）细胞内糖酵解的抑制剂;（3）AMPK途径的刺激剂;（4）沉默调节蛋白激活剂;（5）mTOR途径的抑制剂，和（6）多胺。几家生物技术公司已经成立，以追求这些战略中的几个。这篇综述的目的是描述针对糖酵解抑制的方法。这种上游策略被认为是一种有效的手段，调用广泛的抗衰老机制诱导CR。抗癌和抗肥胖作用是早期开发工作中的重要考虑因素。虽然可以讨论许多候选化合物，但选择审查的化合物如下：2-脱氧葡萄糖、3-溴丙酮酸、白杨素、染料木素、甘草酸、白藜芦醇、葡糖胺、甘露庚酮糖和d-阿洛酮糖。一些候选人已经进行了广泛的调查，有正面和负面的结果，而另一些人才刚刚开始研究。
Calorie restriction mimetics encompass a growing research field directed toward developing treatments that mimic the anti-aging effects of long-term calorie restriction without requiring a change in eating habits. A wide range of approaches have been identified that include (1) intestinal inhibitors of fat and carbohydrate metabolism; (2) inhibitors of intracellular glycolysis; (3) stimulators of the AMPK pathway; (4) sirtuin activators; (5) inhibitors of the mTOR pathway, and (6) polyamines. Several biotech companies have been formed to pursue several of these strategies. The objective of this review is to describe the approaches directed toward glycolytic inhibition. This upstream strategy is considered an effective means to invoke a wide range of anti-aging mechanisms induced by CR. Anti-cancer and anti-obesity effects are important considerations in early development efforts. Although many dozens of candidates could be discussed, the compounds selected to be reviewed are the following: 2-deoxyglucose, 3-bromopyruvate, chrysin, genistein, astragalin, resveratrol, glucosamine, mannoheptulose, and d-allulose. Some candidates have been investigated extensively with both positive and negative results, while others are only beginning to be studied.